Quality control in a centralized reconstitution unit of cytotoxic agents: Determination of etoposide using high-performance thin-layer chromatography

Abstract

Introduction. The introduction of a Quality Assur ance Program in the Centralized Reconstitution of Cytotoxic Drugs Unit (CRCDU) at the Arnaud de Villeneuve Hospital Medical Center of Montpellier (France) led to revising our procedures and guide lines. On the average, 170 cytotoxic agents are pre pared weekly, including 20 to 30 preparations of ETOPOSIDE (VP 16). As a quality indicator, we chose etoposide concentration in the final product prepara tion because this drug is viscous and homogenizes poorly in solution. We therefore assumed that etopo side preparation quality should reveal good manufac turing guideline compliance.

Methods. A High-Performance Thin Layer Chro matography (HPTLC) method was selected because it's simple, results can be obtained rapidly, and does not require destruction of a whole preparation. Con centrations were determined by a technique using Silica gel plates (MERCK 60 F 254). Migration solvent was composed of ethyl acetate, methanol, dichloro methane, and aqueous ammonia (170:30:20:10). An optical scanning photodensitometer was set at 220 nm. Each sample was determined in duplicate. Devi ations between theoretical and actual doses were evaluated in terms of pharmaceutical quality related with clinical significance. Results are discussed weekly to determine whether guidelines are consis tent or if a change is necessary.

Results. Eighteen months after implementing, this procedure, its viability as a quality control was tested. 75.9% of samples showed less than 10 percent deviation from theoretical dosage concentration and this is considered a clinically tolerated error by the physicians of our hospital.

Conclusion. In consequence, we feel that using this method is an appropriate quality indicator.